Background: Pain management is a critical but complex issue for the relief of acute pain, particularly for postoperative pain and severe pain in cancer patients. It also plays important roles in promoting quality of care. The introduction of pain management decision support systems (PM-DSS) is considered a potential solution for addressing the complex problems encountered in pain management. This study aims to investigate factors affecting acceptance of PM-DSS from a nurse anesthetist perspective. Methods: A questionnaire survey was conducted to collect data from nurse anesthetists in a case hospital. A total of 113 questionnaires were distributed, and 101 complete copies were returned, indicating a valid response rate of 89.3%. Collected data were analyzed by structure equation modeling using the partial least square tool. Results: The results show that perceived information quality (γ=.451, p<.001), computer self-efficacy (γ=.315, p<.01), and organizational structure (γ=.210, p<.05), both significantly impact nurse anesthetists’ perceived usefulness of PM-DSS. Information quality (γ=.267, p<.05) significantly impacts nurse anesthetists’ perceptions of PM-DSS ease of use. Furthermore, both perceived ease of use (β=.436, p<.001, R2=.487) and perceived usefulness (β=.443, p<.001, R2=.646) significantly affected nurse anesthetists’ PM-DSS acceptance (R2=.640). Thus, the critical role of information quality in the development of clinical decision support system is demonstrated. Conclusions: The findings of this study enable hospital managers to understand the important considerations for nurse anesthetists in accepting PM-DSS, particularly for the issues related to the improvement of information quality, perceived usefulness and perceived ease of use of the system. In addition, the results also provide useful suggestions for designers and implementers of PM-DSS in improving system development.